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Conventional cytotoxic management of leukemia has less than optimal results, while it is associated,vith life-threatening toxic effects due to lack of specificity for hematopoietic cells. Therefore, novel therapeutic strategies with monoclonal antibodies (MAbs) are being explored for delivering chemotherapy or radiation directly to malignant cells. Recently, anti-CD33 antibodies have been engineered to target malignant myeloid and immature normal cells and have been used to deliver cytotoxic agents or radiation to leukemic cells. 131I-labeled anti-CD45 antibodies are used in combination with conventional chemotherapy in leukemic patients receiving marrow transplantation. Additionally, the emergence of Rituximab (against CD20) and Campath-1H (against CD52) for chronic lymphocytic leukemia (CLL) has provided encouraging clinical results for the prognosis of this disease. In conclusion, there has been ongoing research indicating that the approach of patients with leukemia through the application of MAbs might be safer and more effective than current treatment. Considering the preliminary data, MAb therapy appears to be a new, promising weapon in the oncologist’s armentarium.